Epithelial Membrane Protein 2 Suppresses Non-Small Cell Lung Cancer Cell Growth by Inhibition of MAPK Pathway

Abstract

Epithelial membrane proteins (EMP1-3) are involved in epithelial differentiation and carcinogenesis. Dysregulated expression of EMP2 was observed in various cancers, but its role in human lung cancer is not yet clarified. In this study, we analyzed the expression of EMP1-3 and investigated the biological function of EMP2 in non-small cell lung cancer (NSCLC). The results showed that lower expression of EMP1 was significantly correlated with tumor size in primary lung tumors (p = 0.004). Overexpression of EMP2 suppressed tumor cell growth, migration, and invasion, resulting in a G1 cell cycle arrest, with knockdown of EMP2 leading to enhanced cell migration, related to MAPK pathway alterations and disruption of cell cycle regulatory genes. Exosomes isolated from transfected cells were taken up by tumor cells, carrying EMP2-downregulated microRNAs (miRNAs) which participated in regulation of the tumor microenvironment. Our data suggest that decreased EMP1 expression is significantly related to increased tumor size in NSCLC. EMP2 suppresses NSCLC cell growth mainly by inhibiting the MAPK pathway. EMP2 might further affect the tumor microenvironment by regulating tumor microenvironment-associated miRNAs.

Fibulin 2 Is Hypermethylated and Suppresses Tumor Cell Proliferation through Inhibition of Cell Adhesion and Extracellular Matrix Genes in Non-Small Cell Lung Cancer

“…As a FBLN family member, FBLN2 has been identified as one of the potential downstream target genes of the tumor suppressor HOPX [ 30 , 31 ]. FBLN2 has been to be upregulated more than 8-fold in HOPX overexpressing cells, compared to mock cells ( Supplementary Table S1 , [ 32 ]). It was reported that FBLN2 exerts a tumor suppressive function in nasopharyngeal cancer (NPC) [ 15 ], breast cancer [ 33 ] and gastric cancer [ 19 ].…”

“…The number of migrated cells was counted in six randomly selected fields. Matrigel-coated transwell chambers (BD Biosciences, Heidelberg, Germany) were applied for the invasion assay [ 32 ]. Cells transfected with the empty vector were used as control.…”

“…Cell culture, collection of the cell culture medium, and exosome isolation were carried out as previously described [ 32 ]. Isolated exosomes (5 ng) were characterized by WB.…”

Characterization of microRNA Profiles in Pasteurella multocida-Infected Rabbits and Identification of miR-29-5p as a Regulator of Antibacterial Immune Response

“…EMP2 is aberrantly upregulated in multiple human cancers, including 63% of invasive breast cancers ( 57 ). EMP2 also suppresses non-small cell lung cancer cell growth by inhibition of MAPK pathway ( 58 ). Additionally, EMP2 modulates innate immune cell population recruitment at the maternal-fetal interface ( 55 ).…”

Tumor‐derived exosomes: Key players in non‐small cell lung cancer metastasis and their implication for targeted therapy

“…(B) Detection of the exosome markers CD63 and CD9 in the exosomes isolated from the normal lung tissues by Western blot analysis. Detailed information about exosome isolation and Western blot analysis was descried previously 41 . Exo, exosomes; GAPDH, glyceraldehyde 3‐phosphate dehydrogenase; TEM, transmission electron microscopy…”